Hepatocyte Transplantation to the Liver via the Splenic Artery in a Juvenile Large Animal Model.

Hepatocyte transplantation (HcTx) is a promising approach for the treatment of metabolic diseases in newborns and children. The most common application route is the portal vein, which is difficult to access in the newborn. Transfemoral access to the splenic artery for HcTx has been evaluated in adults, with trials suggesting hepatocyte translocation from the spleen to the liver with a reduced risk for thromboembolic complications. Using juvenile Göttingen minipigs, we aimed to evaluate feasibility of hepatocyte transplantation by transfemoral splenic artery catheterization, while providing insight on engraftment, translocation, viability, and thromboembolic complications. Four Göttingen Minipigs weighing 5.6 kg to 12.6 kg were infused with human hepatocytes (two infusions per cycle, 1.00E08 cells per kg body weight). Immunosuppression consisted of tacrolimus and prednisolone. The animals were sacrificed directly after cell infusion (n=2), 2 days (n=1), or 14 days after infusion (n=1). The splenic and portal venous blood flow was controlled via color-coded Doppler sonography. Computed tomography was performed on days 6 and 18 after the first infusion. Tissue samples were stained in search of human hepatocytes. Catheter placement was feasible in all cases without procedure-associated complications. Repetitive cell transplantations were possible without serious adverse effects associated with hepatocyte transplantation. Immunohistochemical staining has proven cell relocation to the portal venous system and liver parenchyma. However, cells were neither present in the liver nor the spleen 18 days after HcTx. Immunological analyses showed a response of the adaptive immune system to the human cells. We show that interventional cell application via the femoral artery is feasible in a juvenile large animal model of HcTx. Moreover, cells are able to pass through the spleen to relocate in the liver after splenic artery infusion. Further studies are necessary to compare this approach with umbilical or transhepatic hepatocyte administration.

Radiation exposure of adrenal vein sampling: a German Multicenter Study

Objective: Adrenal vein sampling (AVS) represents the current diagnostic standard for subtype differentiation in primary aldosteronism (PA). However, AVS has its drawbacks. It is invasive, expensive, requires an experienced interventional radiologist and comes with radiation exposure. However, exact radiation exposure of patients undergoing AVS has never been examined. Design and Methods: We retrospectively analyzed radiation exposure of 656 AVS performed between 1999 and 2017 at four university hospitals. The primary outcomes were dose area product (DAP) and fluoroscopy time (FT). Consecutively the effective dose (ED) was approximately calculated. Results: Median DAP was found to be 32.5 Gy*cm2 (0.3­3181) and FT 18 min (0.3­184). The calculated ED was 6.4 mSv (0.1­636). Remarkably, values between participating centers highly varied: Median DAP ranged from 16 to 147 Gy*cm2, FT from 16 to 27 min, and ED from 3.2 to 29 mSv. As main reason for this variation, differences regarding AVS protocols between centers could be identified, such as number of sampling locations, frames per second and the use of digital subtraction angiographies. Conclusions: This first systematic assessment of radiation exposure in AVS not only shows fairly high values for patients, but also states notable differences among the centers. Thus, we not only recommend taking into account the risk of radiation exposure, when referring patients to undergo AVS, but also to establish improved standard operating procedures to prevent unnecessary radiation exposure.

Computed tomography-based survey of the vascular anatomy of the juvenile Göttingen minipig.

Over the past 50 years, image-guided procedures have been established for a wide range of applications. The development and clinical translation of new treatment regimens necessitate the availability of suitable animal models. The juvenile Göttingen minipig presents a favourable profile as a model for human infants. However, no information can be found regarding the vascular system of juvenile minipigs in the literature. Such information is imperative for planning the accessibility of target structures by catheterization. We present here a complete mapping of the arterial system of the juvenile minipig based on contrast-enhanced computed tomography. Four female animals weighing 6.13 ± 0.72 kg were used for the analyses. Imaging was performed under anaesthesia, and the measurement of the vascular structures was performed independently by four investigators. Our dataset forms a basis for future interventional studies in juvenile minipigs, and enables planning and refinement of future experiments according to the 3R (replacement, reduction and refinement) principles of animal research.

Hepatic arterial infusion with oxaliplatin and 5-FU/folinic acid for advanced biliary tract cancer: a phase II study.

BACKGROUND: Effective and tolerable chemotherapy with gemcitabine and cisplatin for advanced biliary tract cancer (BTC) has been established recently. However, overall prognosis is still poor, and additional therapeutic approaches are needed for patients with locally advanced, irresectable and/or pretreated tumors. Hepatic arterial infusion (HAI) of chemotherapy represents a safe and well-established treatment modality, but data on its use in patients with BTC are still sparse. METHODS: Patients with irresectable BTC predominant to the liver were included in a prospective, open phase II study investigating HAI provided through interventionally implanted port catheters. Intraarterial chemotherapy consisted of biweekly oxaliplatin (O) 85 mg/m(2) and folinic acid (F) 170 mg/m(2) with 5-FU (F) 600 mg/m(2). RESULTS: Between 2004 and 2010, 37 patients were enrolled. A total of 432 cycles of HAI were applied with a median of 9 (range 1-46) cycles. Objective response rate was 16 %, and tumor control was achieved in 24 of 37 (65 %) patients. Median progression-free survival was 6.5 months (range 0.5-26.0; 95 % CI 4.3-8.7), median overall survival was 13.5 (range 0.9-50.7; 95 % CI 11.1-15.9) months. The most frequent adverse event was sensory neuropathy grade 1/2 in 10/14 patients. CONCLUSIONS: Using a minimal invasive technique, repetitive HAI with OFF is feasible and results in clinically relevant tumor control with low toxicity in patients with liver predominant advanced BTC.

Splenic artery syndrome after orthotopic liver transplantation: treatment with the Amplatzer vascular plug.

PURPOSE: To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP) for embolization of the splenic artery in patients with hepatic hypoperfusion after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Thirteen patients (9 men and 4 women) with a mean age of 56 years (range 22-70) who developed splenic artery syndrome after OLT with decreased liver perfusion and clinically relevant impairment of liver function (increased transaminase or serum bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were treated by embolization of the proximal third of the splenic artery using the AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F or 8F guiding catheter. RESULTS: The plugs were successfully placed, and complete occlusion of the splenic artery was achieved in all patients. Placement of two plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion took on average 10 min (range 4-35). There was no nontarget embolization or plug migration into more distal segments of the splenic artery. All patients showed improved arterial perfusion, including the liver periphery, on postinterventional angiogram. After embolization, liver function parameters (transaminase and bilirubin levels) improved with normalization of concomitant thrombocytopenia and a decrease in ascites volume. CONCLUSION: Our initial experience in a small patient population with SAS suggests that the AVP enables precise embolization of the proximal splenic artery, thus providing safe and effective treatment for poor liver perfusion after OLT due to SAS.

Hepatic artery calcification in a liver transplant recipient.

The abdominal aorta and the renal, mesenteric, and splenic arteries are frequently affected with arterial wall calcification upon increasing age; the hepatic artery is far less often found to be calcified. We report the case of a liver transplant recipient who presented with a calcified hepatic artery in the liver graft 13 years after transplantation for primary sclerosing cholangitis. Although the etiology of hepatic artery calcification was unknown, underlying causes for calcification may include chronic hemodialysis for renal insufficiency and subsequent secondary hyperparathyroidism, as well as a calcified aneurysms. However, it remained unclear whether hepatic artery calcification had to be considered an epiphenomenon or an original pathology of the liver. It thus seems unlikely that hepatic artery calcification as a single finding is to be considered a serious pathologic entity, even for a liver graft.

Embolization of experimental wide-necked aneurysms with iodine-containing polyvinyl alcohol solubilized in a low-angiotoxicity solvent.

BACKGROUND AND PURPOSE: To evaluate the ready-to-use iodine-containing polyvinyl alcohol (I-PVA) dissolved in the low angiotoxic solvent N-methyl pyrrolidone (NMP) for embolization of porcine wide-necked aneurysms. METHODS: Fourteen broad-based carotid sidewall aneurysms were surgically constructed in 7 swine. I-PVA (40%) in NMP was injected under temporary balloon occlusion bridging the aneurysm neck. After 4 weeks, follow-up angiography, multisection CT angiography (MSCTA), and 3T MR imaging including MR angiography (MRA) sequences were performed. Afterward, harvested aneurysms were investigated histopathologically. RESULTS: The liquid embolic was well visible under fluoroscopy and displayed a favorable precipitation pattern, allowing for controlled polymer delivery. Ten aneurysms (71%) were initially completely occluded, whereas in 1 aneurysm, a minimal polymer leakage was observed. The other 4 aneurysms (29%) were almost completely occluded. One animal suffered a lethal rebleeding from the anastomosis after uneventful embolization. Aneurysms embolized with I-PVA could be discriminated well from the parent artery without beam-hardening artifacts on MSCTA, and no susceptibility artifacts were encountered on MR imaging. Histologic examination revealed all aneurysms covered with a membrane of fibroblasts and an endothelial cell layer while a moderate intraaneurysmal inflammatory response to the polymer was observed. CONCLUSION: I-PVA dissolved in NMP has proved its effectiveness for the embolization of experimental wide-necked aneurysms. This precipitating liquid embolic offers several interesting features in that it needs no preparation before use and no radiopaque admixtures, the latter allowing for artifact-free evaluation of treated aneurysms with MSCTA and MRA. Moreover, it uses NMP as a solvent, which has only a low angiotoxicity.

Percutaneous transjugular direct porto-caval shunt in patients with Budd-Chiari syndrome.

The purpose of the study was to evaluate the feasibility and effectiveness of direct porto-caval shunts in patients with Budd-Chiari syndrome (BCS) in whom there is no access to the hepatic veins during transjugular intrahepatic portosystemic shunt (TIPSS). We included six consecutive patients with fulminant/acute Budd-Chiari syndrome (mean age: 35 years) in whom a conventional TIPSS was not possible due to inaccessible hepatic veins. We performed a direct porto-caval shunt via a transhepatic approach. Patients were followed up by means of clinical examination, laboratory investigations, and Doppler ultrasound. TIPSS implantation from the inferior vena cava (IVC) was successful in all six patients (100%). The median transhepatic shunt length was 9 cm (8-10 cm). No procedure-related complications were observed in our patients. Early shunt occlusion occurred in three out of six patients (50%). In all three of these patients, the stent used to stabilize the shunt ended 1-2 cm before reaching the IVC. All occlusions were successfully recanalized. One of these patients developed recurrent early shunt as well as mesenteric and splenic vein occlusions. She died 7 days after TIPSS placement due to an unmanageable coagulation disorder. The remaining five patients were followed up by planned clinical examination and laboratory investigations (mean follow-up time was 15 months; patient 1 was followed up for 13 months, patient 2 for 14 months, patient 3 for 15 months, and patients 4 and 5 for 16 months) and all displayed a complete and durable resolution of liver failure and ascites without reintervention. In patients with acute liver failure originating from BCS and inaccessible hepatic veins, a direct transhepatic porto-caval shunt can be performed safely and effectively under ultrasound guidance. Future studies in larger patient groups should investigate if the patency of transcaval TIPSS with long transhepatic shunt segments is similar compared to conventional TIPSS via the hepatic vein.

[Ultrasound- and fluoroscopy-guided implantation of peripherally inserted central venous catheters (PICCs)]. / Ultraschall- und durchleuchtungsgesteuerte Implantation peripher inserierter zentral-venöser Katheter (PICC).

PURPOSE: Evaluation of ultrasound- and fluoroscopy-guided implantation of peripherally inserted central venous catheters (PICCs). MATERIALS AND METHODS: In 32 patients (12 males, 20 females; mean age 64.1 +/- 11.9 years) with clinical indication for long term central venous catheter (chemotherapy: N = 5; parenteral nutrition and fluid substitution: N = 26; parenteral pain therapy: N = 1) a PICC was placed by an interventional radiologist using ultrasound guidance. RESULTS: The placement of the PICC was technically successful in 31 (96.9%) patients, with placement of 20 single-lumen 5F PICCs, 4 double-lumen 6F PICCs and 7 double-lumen 7F PICCs. The mean duration of catheter usage was 28.4 (2 - 161) days with a total of 910 catheter days. No catheter occlusions were recorded. Two patients developed a superficial venous thrombosis of the upper extremity. The resulting thrombotic rate was 2.2 per 1000 catheter days. No catheter associated infection was recorded. CONCLUSION: The ultrasound guided placement of peripherally inserted central venous catheters (PICCs) via a superficial vein of the upper extremity is a practical alternative to central catheters via central veins.

[Radiological-guided liver-port implantation: Evaluation, technical approach, interventional procedure and follow up]. / Radiologisch-interventionelle Leberportanlage: Evaluierung, Zugangswege, Intervention und Nachkontrolle.

UNLABELLED: Radiological-guided liver-port implantation: Evaluation, technical approach, interventional procedure and follow up. PURPOSE: Description of evaluation, technical approach, interventional procedure and follow up of radiological-guided liver-port implantation. METHOD: Percutaneous implantation of a liver-port system was performed in twelve patients through a transfemoral approach and in one patient via the superficial epigastric artery after surgical exploration. In four patients we used port systems which are accessible via ventral puncture. Strecker-port systems were implanted in the remaining nine patients. RESULTS: The liver-port implantation was technically successful in all cases. No dislocation of the distal catheter tip, no thrombosis of the hepatic or splenic artery, no leakage near connections of the catheters or connections of catheter and port system and no thrombosis of the femoral arteries were observed. Correction of a kink in the catheter was performed in one patient. Another patient showed prolonged healing of the subcutaneous pocket. CONCLUSIONS: Interventional liver-port implantation is a safe procedure and leads to good clinical results. From the view of the radiologist the Strecker-system shows a good performance. The approach via the superficial epigastric artery demands excellent interdisciplinary cooperation.

Liver transplantation for treatment of intrahepatic Osler's disease: first experiences.

BACKGROUND: Intrahepatic Osler's disease with multiple arteriovenous malformations and high intrahepatic shunting may lead to secondary pulmonary hypertension followed by right-heart stress and insufficiency. Until now, therapy with arterial embolization, banding, or ligation of the hepatic arteries is still limited and provides unsatisfactory long-term results. Liver transplantation offers another therapeutic option. METHODS: We report on four patients with intrahepatic involvement of Osler's disease who were liver transplanted between 1995 and 1999. All patients suffered from restricted liver function and right-heart insufficiency with multiple cardiac decompensations. One patient received one course of embolization, and another received six courses of embolization and then banding of the main hepatic artery before transplantation. In both patients, the clinical symptoms improved for only a few months. RESULTS: All patients had high degrees of intrahepatic arteriovenous shunting, and cardiac output measurements were between 8.0 to 13.3 L/min preoperatively. Preoperative mean pulmonary artery pressure was between 24 to 35 mmHg. After liver transplantation, cardiac output and right-heart diameter decreased or normalized and pulmonary pressure reached the normal range after 2 months. All patients received tacrolimus and steroids for primary immunosuppression. In one case, temporary hemodialysis was necessary for 2 weeks after transplantation, but renal function recovered completely. After follow-up time of 12 to 65 months, all patients had normal graft function and good cardiopulmonary condition. CONCLUSIONS: Indication for liver transplantation should be considered in patients with intrahepatic Osler's disease, high arteriovenous shunting with right-heart stress, and restricted liver function before irreversible fixed pulmonary hypertension leads to severe right-heart insufficiency or failure. Our therapeutic regimen of early liver transplantation in the case of intrahepatic Osler's disease in four patients has promising results.

[Revascularization of the aortoiliac arteries using stents]. / Revaskularizace v aortoilických tepnách pomocí stentu.

The authors summarised their three year experience with endovascular treatment of the aortoiliac artery obstructive lesions using stents and transluminal angioplasty. Fifty-seven patients (61 limbs) underwent stent implantation to treat claudications (n = 50 limbs), rest pain (n = 6), non-healing defects (n = 4) and one patient was asymptomatic (n = 1). After stent placement patients were followed-up using clinical and duplex ultrasound examinations at 3 months and 6 months thereafter. Immediate angiographic success was achieved in all cases. Three serious complications were observed. Percutaneous reinterventions because of stenosis inside the stent were performed in 7 patients (7 limbs). The primary patency rates were 92% at 1 year, 88% at 2 years and 86% at 3 years. Cumulative primary assisted patency were 98% (mean follow-up 15.8 months, range 3-47 months). Regular clinical and ultrasound follow-up examinations can reveal the asymptomatic instent stenosis and percutaneous reinterventions can improve long-term stent patency.

Young Investigator Award presentation at the 13th annual meeting of the ESMRMB, September 1996, Prague. Quantification of pulmonary water compartments by magnetic resonance.

The purpose of this study was to quantify pulmonary water compartments of total, intravascular, and extravascular lung water in excised and perfused sheep lungs with the use of magnetic resonance imaging techniques. Total lung water was measured by proton density maps calculated from multi-spin-echo images. Intravascular lung water was evaluated by magnetic resonance angiography before and after injection of gadolinium diethylenetriamine penta-acetic acid polylysine, a macromolecular paramagnetic contrast agent. Intravascular lung water was calculated from signal intensity histogram changes comparing pre- and postcontrast angiograms. Extravascular water was calculated as the difference between total and intravascular lung water. Quantities of total and intravascular lung water measured by magnetic resonance techniques were compared to reference results obtained from wet/dry weight gravimetry and Evans blue dilution performed after imaging. Magnetic resonance and reference results correlated significantly (total lung water: r = 0.93, p < 0.001; intravascular lung water: r = 0.80, p < 0.001; extravascular lung water: r = 0.89, p < 0.001). Therefore, we conclude that quantitative magnetic resonance techniques are potentially useful for the clinical evaluation of pulmonary water compartments.

Epidural lipomatosis: case report and literature review.

We report a case of symptomatic epidural lipomatosis in a 36-year-old man following a heart lung transplant and 3.5 years of steroid medication. A review of the pertinent literature emphasises the importance of including this diagnosis in the differential diagnosis of patients receiving steroid medication or markedly obese patients with back pain or symptoms suggesting spinal cord or cauda equina compression.

[Preoperative staging of bladder carcinomas with Gd-DTPA-supported dynamic magnetic resonance tomography. Comparison with plain and Gd-DTPA-supported spin-echo sequences]. / Präoperatives Staging von Blasenkarzinomen mit der Gd-DTPA-unterstützten dynamischen Magnetresonanztomographie. Vergleich mit nativen und Gd-DTPA-unterstützten Spin-Echo-Sequenzen.

PURPOSE: Evaluation of dynamic Gd-DTPA enhanced MR imaging in the staging of bladder cancer. METHODS: We studied 40 patients with histologically proven bladder cancer. All patients were examined with routine T1- and T2-weighted MRI and late Gd-DTPA enhanced T1-weighted MRI. Additionally, a dynamic study was performed with 10 subsequent short FLASH-2-D gradient echo sequences without delay immediately after bolus injection of Gd-DTPA. Signal intensities of the tumour and of the surrounding tissue as well as image contrast parameters were quantified. RESULTS: The dynamic study showed a higher accuracy in the evaluation of stage pTa to pT2 cancer compared to spin echo MRI (63% and 46%, respectively) and no difference regarding the sensitivity (87.5%). However, overstaging was a problem with both modalities. The contrast-to-noise ratio of bladder tumour and muscle was equal or significant higher with the dynamic study compared to spin echo MRI. A higher signal-to-contrast ratio of bladder tumour and bladder muscle was calculated for the dynamic study compared with the spin-echo MRI (p < 0.01; Mann-Whitney U test). CONCLUSION: Dynamic Gd-DTPA enhanced MRI is recommended to be used additionally in the preoperative staging of bladder neoplasms.

[The role of the exercise test in patients with ischemic heart disease in estimating the risk of sudden death]. / Prínos pracovního testu u nemocných s ischemickou chorobou srdecní k odhadu rizika náhlé smrti.

The authors evaluated after 4-year interval the results of coronarographic and spiroergometric examination after a work load on a bicycle ergometer up to the limiting work syndrome in 51 all patients with the aim to reveal "risk factors" of sudden death in CHD patients. The following parameters were recorded: age, duration of treatment number of cigarettes smoked, systolic blood pressure at rest and the daily dose of the most frequently used drugs. After the work load the limiting values of pulse rate, systolic blood pressure, oxygen consumption, blood lactate level and the work ECG were evaluated. In the group of 7 sudden deaths of CHD patients the authors found statistically significant (p less than 0.001) a lower mean limiting value of oxygen consumption/kg and a deeper (p less than 0.0001) mean depression of the S-T segment in the work ECG when compared with 35 CHD patients surviving for 4 years. Both indicators are considered the main "risk factors" for sudden death.

[Results of surgical treatment of aortic coarctation]. / Výsledky chirurgické lécby koarktace aorty.

The authors summarize the results of surgical treatment of coarctation of the aorta in 98 patients. Te group comprised 70 children aged 3 to 15 years and 28 adults. The most frequently used technique was resection of the coarctation with a direct end-to-end anastomosis. It was used in a total of 83 patients. Three patients died, i. e. 3.1%. Of 32 patients who were invited for a check-up examination 16 came. Three of them had undergone a plastic operation with a dacron patch. All were subjected to angiographic examination in a lateral projection by injection of the contrast substance into the aortal arch and pressure readings were taken in the aorta above and below the site of anastomosis. Residual gradients were found in three patients (10, 12, 20 torr). Hypertension persists in 6 patients. In four patients slight stenosis of the aorta was found without a gradient, in one patient a small pseudoaneurysm. None of the findings called for further surgical intervention.

Cyanoacrylates: an ideal agent for intravascular embolotherapy?

From a large number of various embolic agents introduced in interventional radiology in last two decades it seems that an ideal embolic agent for intravascular embolization has not been found yet. The favourable properties of one of these agents - n-butyl 2-cyanoacrylate are presented by authors. It is concluded that the intravascular embolotherapy with n-butyl 2-cyanoacrylate performed in a strict accordance with the technical demands has proved to be efficient in the management of symptomatic arteriovenous malformations, in the percutaneous transhepatic embolization of gastroesophageal varices and in palliative embolization of renal tumors.